FDA Approves First Oral Therapy Voclosporin for Lupus Nephritis

The US Food and Drug Administration (FDA) has approved voclosporin (LUPKYNIS, Aurinia Pharmaceuticals) for the treatment of lupus nephritis (LN), a condition that is associated with kidney damage, kidney failure, cardiac events, and death. Voclosporin, the first FDA-approved oral therapy for this condition, has shown significantly improved renal response rates when compared with standard therapies.

Currently, 200,000-300,000 people in the United States are living with LN, a serious complication of systemic lupus erythematosus (SLE), with the disease disproportionately affecting Black, Asian, and Hispanic individuals. Voclosporin, in combination with an existing immunosuppressive therapy regimen, works to safely and effectively treat adult patients with LN.

The development of voclosporin stemmed from Aurinia’s existing clinical studies in LN: the AURORA Phase 3 study and the AURA-LV Phase 2 study. Over the course of 52 weeks, patients receiving voclosporin had vastly improved outcomes when taken in combination with standard-of-care therapy (SoC), mycophenolate mofetil (MMF), and low dose steroids.

For both Phase 2 and 3 studies, 533 patients with LN were given voclosporin 23.7 mg or a placebo twice a day in conjunction with SoC and a MMF target dose of 2 g daily. For the first 2 days, patients received intravenous (IV) methylprednisolone (up to 1 g), with a taper of oral corticosteroids after that. Oral prednisone dosage was 20 mg/day for patients weighing <45 kg and 25 mg/day for patients ≥45 kg. By week 16, their target goal was a dose of 2.5 mg/day. Patients (Class III, IV or V) were required to have baseline eGFR >45 mL/min/1.73 m².

The phase 3 study demonstrated that voclosporin was twice as effective at achieving a complete renal response than the SoC group. Patients also obtained a 50% reduction in urine protein creatinine ratio (UPCR), the measurement used to monitor protein in the kidneys, twice as fast with more achieving a complete renal response by 24 weeks when compared with SoC. Early intervention and kidney response (marked by UPCR) have been historically linked to better outcomes and prevention of kidney damage. The study found that patients receiving voclosporin had improved response rates across all classes of LN.

Common side effects (>3%) included a decrease in glomerular filtration rate, hypertension, diarrhea, headache, anemia, cough, urinary tract infection, abdominal pain, dyspepsia, alopecia, renal impairment, mouth ulceration, fatigue, tremor, acute kidney injury, and decreased appetite.

Aurinia Pharmaceuticals has recently launched Aurinia Alliance, a support program, to help patients and physicians learn more about voclosporin, including how to navigate insurance and medication costs.

Up until this point, treating patients with LN has been incredibly challenging as the limited therapies available have been shown to be highly toxic and not significantly effective. “The [voclosporin] approval marks a turning point for the lupus nephritis community – patients, caregivers, families, and healthcare professionals – all of whom we thank for their partnership in the development of this innovative novel treatment," Peter Greenleaf, president and chief executive officer of Aurinia Pharmaceuticals, said in a statement. "We are thrilled to bring [voclosporin] to the people impacted by this devastating condition.”